rs4597022

Positions:

• chr10-43389772-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098204.2(HNRNPF):​c.-52-1836G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,014 control chromosomes in the GnomAD database, including 10,766 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (10766 hom., cov: 32)
• Consequence: HNRNPF NM_001098204.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

Genes affected

HNRNPF (HGNC:5039): (heterogeneous nuclear ribonucleoprotein F) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins that complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and regulate alternative splicing, polyadenylation, and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has three repeats of quasi-RRM domains that bind to RNAs which have guanosine-rich sequences. This protein is very similar to the family member hnRPH. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNRNPF	NM_001098204.2	c.-52-1836G>C		intron_variant		ENST00000682386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNRNPF	ENST00000682386.1	c.-52-1836G>C		intron_variant			NM_001098204.2	P1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52390 AN: 151896 Hom.: 10740 Cov.: 32

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.345 AC: 52466 AN: 152014 Hom.: 10766 Cov.: 32 AF XY: 0.346 AC XY: 25671 AN XY: 74296

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.305

Alfa AF: 0.297 Hom.: 1012

Bravo AF: 0.357

Asia WGS AF: 0.329 AC: 1144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4597022; hg19: chr10-43885220;